π-Expanded Ketocoumarins as Efficient, Biocompatible Initiators for Two-Photon-Induced Polymerization

Abstract

A series of π-expanded coumarins comprising of 4–5 conjugated rings were designed and synthesized. The strategic placement of two dialkylamino groups containing long alkyl chains attached to the peripheral ends of bis-coumarins resulted in dyes with superb solubility. As α,β-unsaturated ketones, these compounds display properties of donor–acceptor–donor (D–A–D)-type chromophores. Photophysical studies of the new functional dyes revealed a combination of favorable properties: strong absorption of blue and green light, weak fluorescence, reasonable two-photon absorption (2PA) cross-section, and complete solubility in nonpolar solvents. The fluorescence lifetimes of coumarin-derived α,β-unsaturated ketones were measured for the first time. The placement of two amine groups at peripheral positions of the dyes produced two-photon absorption cross-section values at the level of 150–400 GM around 800 nm, which generated two-photon photoinitiation. The highest 2PA cross-section was approximately 400 GM for the derivative of 4-methylcyclohexanone. Directly using these compounds as sensitizer or initiator, two (2D)- and three-dimensional (3D) nanopatterns were successfully fabricated by two-photon initiated polymerization. 3,3′-Carbonyl-biscoumarin, which contains two dihexylamino substituents at positions 7 and 7′ possesses the largest fabrication window. MC3T3-E1 preosteoblastic cells exhibited strong adherence to all π-expanded coumarins and the same spindle-shaped morphology as the tissue culture treated polystyrene control surface. Additionally, our results showed an increase in cell proliferation after 3 and 7 days in culture, as well as a high cell viability of approximately 100% on all materials compared to the control surface. These findings confirm that D–A–D-type ketocoumarin derivatives used as potential photoinitiators are noncytotoxic and can be used in the fabrication of biomaterial scaffolds for tissue engineering applications.